My research interest lies in understanding the pathophysiologic mechanisms of diabetic vascular complications and identifying new drug development targets. One of the diseases that I focus on is preeclampsia (PE) within the context of diabetes. PE is characterized as diffuse vascular constriction (manifested as hypertension) accompanied by kidney dysfunction occurring after 20 weeks’ gestation. Currently there is no effective treatment and delivery is the only “cure”. Pregnancy in women with diabetes is associated with a dramatic (~4 fold) increase of PE, but the underlying mechanism is unclear. With the help of many co-investigators and collaborators, we have recruited a longitudinal, multi-center cohort of Type 1 diabetic pregnant women. About 20% of them developed PE, as compared with only 4% in non-diabetic pregnancy controls. Currently we are conducting extensive investigation on this unique cohort, and testing various potential mechanisms including anti-angiogenic, inflammatory and endothelial factors in the plasma and tissue samples. It is of interest that some of the factors are also involved with other diabetic vascular complications such as diabetic wound, and represent new drug development opportunities. Our ultimate goal is to discover reliable predictors for early detection of the highest risk diabetic patients, and to develop new therapeutics.

A second focus of my research is to understand why retinal capillary pericytes demise at the very early stages of diabetic retinopathy. We have found that cultured human retinal pericyte undergo apoptosis after being treated with oxidized and glycated LDL. These conditions are to simulate the dyslipoproteinemia occurring in diabetic humans. Our recent gene array study in human retinal pericytes revealed a total of 60 genes whose expression levels are significantly altered in response to modified LDL. These genes belong to several families and pathways that are critical to lipid, inflammation and oxidative stress regulation. Our objective is to dissect out these pathways and to identify and validate new targets for drug development.

Besides these, I am also involved with the collaboration with DCCT/EDIC and VA Diabetes Trial, studies that aim to identify risk factors and new makers in prediction of diabetic vascular complications in Types 1 and 2 diabetes.

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